tbuckley/cabot-search huggingface dataset:
Artificial Neural Processing‐Driven Bioelectronic Nose for the Diagnosis of Diabetes and Its Complications
Authors: Woong Bi Jang, Dongwon Yi, Thanh Mien Nguyen, Yujin Lee, Eun Ji Lee, Jaewoo Choi, You Hwan Kim, Eun‐Jung Choi, Jin‐Woo Oh, Sang‐Mo Kwon
Journal: Advanced Healthcare Materials (2023)

Diabetes and its complications affect the younger population and are associated with a high mortality rate; however, early diagnosis can contribute to the selection of appropriate treatment regimens that can reduce mortality. Although diabetes diagnosis via exhaled breath has great potential for early diagnosis, research on such diagnosis is restricted to disease detection, requiring in-depth examination to diagnose and classify diseases and their complications. This study demonstrates the use of an artificial neural processing-based bioelectronic nose to accurately diagnose diabetes and classify diabetic types (type I and II) and their complications, such as heart disease. Specifically, an M13 phage-based electronic nose (e-nose) is used to explore the features of subjects with diabetes at various levels of cellular and organismal organization (cells, liver organoids, and mice). Exhaled breath samples are collected during culturing and exposed to the phage-based e-nose. Compared with cells, liver organoids cultured under conditions mimicking a diabetic environment display properties that closely resemble the characteristics of diabetic mice. Using neural pattern separation, the M13 phage-based e-nose achieves a classification success rate of over 86% for four conditions in mice, namely, type 1 diabetes, type 2 diabetes, diabetic cardiomyopathy, and cardiomyopathy.
Spectrum of Response to Platinum and PARP Inhibitors in Germline <i>BRCA</i>–Associated Pancreatic Cancer in the Clinical and Preclinical Setting
Authors: Chani Stossel, Maria Raitses-Gurevich, Dikla Atias, Tamar Beller, Yulia Glick Gorman, Sharon Halperin, Eyal Peer, Robert E. Denroche, Amy Zhang, Faiyaz Notta, Julie M. Wilson, Grainne M. O'Kane, Elina Haimov Talmoud, Nora Amison, Michael Schvimer, Seth J. Salpeter, Vered Bar, Adi Zundelevich, Itay Tirosh, Rotem Tal, Gal Dinstag, Yaron Kinar, Yonatan Eliezer, Uri Ben-David, Nancy S. Gavert, Ravid Straussman, Steven J. Gallinger, Raanan Berger, Talia Golan
Journal: Cancer Discovery (2023)

Germline BRCA-associated pancreatic ductal adenocarcinoma (glBRCA PDAC) tumors are susceptible to platinum and PARP inhibition. The clinical outcomes of 125 patients with glBRCA PDAC were stratified based on the spectrum of response to platinum/PARP inhibition: (i) refractory [overall survival (OS) <6 months], (ii) durable response followed by acquired resistance (OS <36 months), and (iii) long-term responders (OS >36 months). Patient-derived xenografts (PDX) were generated from 25 patients with glBRCA PDAC at different clinical time points. Response to platinum/PARP inhibition in vivo and ex vivo culture (EVOC) correlated with clinical response. We deciphered the mechanisms of resistance in glBRCA PDAC and identified homologous recombination (HR) proficiency and secondary mutations restoring partial functionality as the most dominant resistant mechanism. Yet, a subset of HR-deficient (HRD) patients demonstrated clinical resistance. Their tumors displayed basal-like molecular subtype and were more aneuploid. Tumor mutational burden was high in HRD PDAC and significantly higher in tumors with secondary mutations. Anti-PD-1 attenuated tumor growth in a novel humanized glBRCA PDAC PDX model. This work demonstrates the utility of preclinical models, including EVOC, to predict the response of glBRCA PDAC to treatment, which has the potential to inform time-sensitive medical decisions. glBRCA PDAC has a favorable response to platinum/PARP inhibition. However, most patients develop resistance. Additional treatment options for this unique subpopulation are needed. We generated model systems in PDXs and an ex vivo system (EVOC) that faithfully recapitulate these specific clinical scenarios as a platform to investigate the mechanisms of resistance for further drug development. This article is highlighted in the In This Issue feature, p. 1749.
Construction of Porous Perovskite Oxide Microrods with Au Nanoparticle Anchor for Precise Metabolic Diagnosis of Alzheimer's Disease
Authors: Heyuhan Zhang, Fangying Shi, Yinghua Yan, Chunhui Deng, Nianrong Sun
Journal: Advanced Healthcare Materials (2023)

Alzheimer's disease (AD) is a progressive illness, and early diagnosis and treatment can help delay its progression. However, clinics still lack high-throughput, low-invasive, precise, and objective diagnostic strategies. Herein, the Au nanoparticles anchored porous perovskite oxide microrods (CTO@Au) with designed superior properties is developed to construct a high-throughput detection platform. Specifically, a single metabolic fingerprinting is obtained from only 30 nL of serum within seconds, enabling the rapid acquisition of 239 × 8 high-quality fingerprints in ≈ 2 h. AD is distinguish from health controls and Parkinson's disease with an area under the curve (AUC) of 1.000. Moreover, eight specific metabolites are identified as a biomarker panel, based on which precise diagnosis of AD is achieved, with an AUC of 1.000 in blind test. The possible relevant pathways and potential mechanism involved in these biomarkers are investigated and discussed. This work provides a high-performance platform for metabolic diagnostic analysis.
The effects of community interventions on unplanned healthcare use in patients with multimorbidity: a systematic review
Authors: Tavleen Wasan, Benedict Hayhoe, Meryem Cicek, Elena Lammila-Escalera, Dasha Nicholls, Azeem Majeed, Geva Greenfield
Journal: Journal of the Royal Society of Medicine (2023)

Objectives To summarise the impact of community-based interventions for multimorbid patients on unplanned healthcare use. The prevalence of multimorbidity (co-existence of multiple chronic conditions) is rapidly increasing and affects one-third of the global population. Patients with multimorbidity have complex healthcare needs and greater unplanned healthcare usage. Community-based interventions allow for continued care of patients outside hospitals, but few studies have explored the effects of these interventions on unplanned healthcare usage. Design A systematic review was conducted. MEDLINE, EMBASE, PsychINFO and Cochrane Library online databases were searched. Studies were screened and underwent risk of bias assessment. Data were synthesised using narrative synthesis. Setting Community-based interventions. Participants Patients with multimorbidity. Main outcome measures Unplanned healthcare usage. Results Thirteen studies, including a total of 6148 participants, were included. All included studies came from high-income settings and had elderly populations. All studies measured emergency department attendances as their primary outcome. Risk of bias was generally low. Most community interventions were multifaceted with emphasis on education, self-monitoring of symptoms and regular follow-ups. Four studies looked at improved care coordination, advance care planning and palliative care. All 13 studies found a decrease in emergency department visits post-intervention with risk reduction ranging from 0 (95% confidencec interval [CI]: –0.37 to 0.37) to 0.735 (95% CI: 0.688–0.785). Conclusions Community-based interventions have potential to reduce emergency department visits in patients with multimorbidity. Identification of specific successful components of interventions was challenging given the overlaps between interventions. Policymakers should recognise the importance of community interventions and aim to integrate aspects of these into existing healthcare structures. Future research should investigate the impact of such interventions with broader participant characteristics.
Helminths' therapeutic potential to treat intestinal barrier dysfunction
Authors: Thomas C. Mules, Stephen Inns, Graham Le Gros
Journal: Allergy (2023)

Abstract The intestinal barrier is a dynamic multi‐layered structure which can adapt to environmental changes within the intestinal lumen. It has the complex task of allowing nutrient absorption while limiting entry of harmful microbes and microbial antigens present in the intestinal lumen. Excessive entry of microbial antigens via microbial translocation due to ‘intestinal barrier dysfunction’ is hypothesised to contribute to the increasing incidence of allergic, autoimmune and metabolic diseases, a concept referred to as the ‘epithelial barrier theory’. Helminths reside in the intestinal tract are in intimate contact with the mucosal surfaces and induce a range of local immunological changes which affect the layers of the intestinal barrier. Helminths are proposed to prevent, or even treat, many of the diseases implicated in the epithelial barrier theory. This review will focus on the effect of helminths on intestinal barrier function and explore whether this could explain the proposed health benefits delivered by helminths.
Editor's Note: Reduced miR-128 in Breast Tumor–Initiating Cells Induces Chemotherapeutic Resistance via Bmi-1 and ABCC5
Authors: Yinghua Zhu, Fengyan Yu, Yu Jiao, Juan Feng, Wei Tang, Herui Yao, Chang Gong, Jianing Chen, Fengxi Su, Yan Zhang, Erwei Song
Journal: Clinical Cancer Research (2023)

Fig. 4D, the scatter plot for SK-3rd cells transduced with shBmi-1 at 1 ADM
MEDI0457 Plus Durvalumab in HPV-associated HNSCC—Response
Authors: Charu Aggarwal, Maozhen Gong, Rakesh Kumar
Journal: Clinical Cancer Research (2023)

We thank Dr. Mori and colleagues for their interest and highlighting the statistical analysis for our study, “Safety and efficacy of MEDI0457 plus durvalumab in patients with human papillomavirus–associated recurrent/metastatic head and neck squamous cell carcinoma” (1). We concluded that, although the combination was well tolerated, the primary endpoint was not met. In the original design of the trial, an objective response rate (ORR) of 30% was used to evaluate and justify the sample size with an H0 ORR ≤ 15% versus Ha ORR > 15% with a power of 80% with one-sided type 1 error = 0.1. Among 29 evaluable patients, 8 patients had a response yielding a formal exact test P value = 0.05858. Given the fact P < alpha, we should have rejected the null hypothesis, and we could conclude that the primary endpoint was met. In addition, as our colleagues point out, since the ORR was 27.6%, and 80% CI of 16.8%–40.9% calculated by the Clopper-Pearson method, null hypothesis could be rejected because the lower limit was more than 15%.However, during a study amendment, we adopted Bayesian predictive probability (2) for continuous monitoring of the trial for efficacy. Per the algorithm, we defined success as P (ORR ≥ 0.30) > 95% and futility as P (ORR ≥ 0.30) < 20%. With these settings, we could prespecify a decision table where a predictive probability of success > 95% would trigger a Go and a predictive probability of futility > 80% would trigger a No-Go. Ultimately, the decision was based on the amended statistical design using Bayesian predictive probability to account for comprehensive monitoring of overall efficacy of the trial. We appreciate the interest of Dr. Mori and colleagues in the research findings and acknowledge that reporting of predictive probability should have been addressed in our article.See the original Letter to the Editor, p. 2735C. Aggarwal reports other support from Genentech, Lilly, Celgene, Merck, AstraZeneca, Blueprint Genetics, Shionogi, Daiichi Sankyo/AstraZeneca, Regeneron/Sanofi, Eisai, BeiGene, Turning Point Therapeutics, Pfizer, Janssen, and Boehringer Ingelheim outside the submitted work. M. Gong reports personal fees from AstraZeneca during the conduct of the study; personal fees from AstraZeneca outside the submitted work. R. Kumar reports employment at AstraZeneca.
Blastic plasmacytoid dendritic cell neoplasm: a comprehensive review in pediatrics, adolescents, and young adults (AYA) and an update of novel therapies
Authors: Branko Cuglievan, Jeremy Connors, Jiasen He, Sajad Khazal, Sireesha Yedururi, Julia Dai, Sofia Garces, Andres E. Quesada, Michael Roth, Miriam Garcia, David McCall, Amber Gibson, Dristhi Ragoonanan, Demetrios Petropoulos, Priti Tewari, Cesar Nunez, Kris M. Mahadeo, Sarah K. Tasian, Adam J. Lamble, Anna Pawlowska, Danielle Hammond, Abhishek Maiti, Fadi G. Haddad, Jayatsu Senapati, Naval Daver, Naseema Gangat, Marina Konopleva, Soheil Meshinchi, Naveen Pemmaraju
Journal: Leukemia (2023)

Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that can involve the bone marrow, peripheral blood, skin, lymph nodes, and the central nervous system. Though more common in older adults, BPDCN has been reported across all age groups, including infants and children. The incidence of pediatric BPDCN is extremely low and little is known about the disease. Pediatric BPDCN is believed to be clinically less aggressive but often with more dissemination at presentation than adult cases. Unlike adults who almost always proceed to a hematopoietic stem cell transplantation in first complete remission if transplant-eligible, the majority of children can be cured with a high-risk acute lymphoblastic leukemia-like regimen. Hematopoietic stem cell transplantation is recommended for children with high-risk disease, the definition of which continues to evolve, or those in relapse and refractory settings where outcomes continue to be dismal. Novel agents used in other hematologic malignancies and CD123 targeted agents, including chimeric antigen receptor T-cells and monoclonal/bispecific antibodies, are being brought into research and practice. Our goal is to provide a comprehensive review of presentation, diagnosis, and treatment by review of pediatric cases reported for the last 20 years, and a review of novel targeted therapies and therapies under investigation for adult and pediatric patients.
Advances of medical nanorobots for future cancer treatments
Authors: Xiangyi Kong, Peng Gao, Jing Wang, Yi Fang, Kuo Chu Hwang
Journal: Journal of Hematology & Oncology (2023)

Early detection and diagnosis of many cancers is very challenging. Late stage detection of a cancer always leads to high mortality rates. It is imperative to develop novel and more sensitive and effective diagnosis and therapeutic methods for cancer treatments. The development of new cancer treatments has become a crucial aspect of medical advancements. Nanobots, as one of the most promising applications of nanomedicines, are at the forefront of multidisciplinary research. With the progress of nanotechnology, nanobots enable the assembly and deployment of functional molecular/nanosized machines and are increasingly being utilized in cancer diagnosis and therapeutic treatment. In recent years, various practical applications of nanobots for cancer treatments have transitioned from theory to practice, from in vitro experiments to in vivo applications. In this paper, we review and analyze the recent advancements of nanobots in cancer treatments, with a particular emphasis on their key fundamental features and their applications in drug delivery, tumor sensing and diagnosis, targeted therapy, minimally invasive surgery, and other comprehensive treatments. At the same time, we discuss the challenges and the potential research opportunities for nanobots in revolutionizing cancer treatments. In the future, medical nanobots are expected to become more sophisticated and capable of performing multiple medical functions and tasks, ultimately becoming true nanosubmarines in the bloodstream.
Correction: Proteogenomic Analysis of Salivary Adenoid Cystic Carcinomas Defines Molecular Subtypes and Identifies Therapeutic Targets
Authors: Renata Ferrarotto, Yoshitsugu Mitani, Daniel J. McGrail, Kaiyi Li, Tatiana V. Karpinets, Diana Bell, Steven J. Frank, Xingzhi Song, Michael E. Kupferman, Bin Liu, J. Jack Lee, Bonnie S. Glisson, Jianhua Zhang, Jon C. Aster, Shiaw-Yih Lin, P. Andrew Futreal, John V. Heymach, Adel K. El-Naggar
Journal: Clinical Cancer Research (2023)

In the original version of this article (1), the Methods section contained two inaccuracies: MYC scoring was stated to be binary (positive, negative) when it was tertiary (high, low, negative), and the positive/negative benchmark for TP63 expression was stated to be at 70% of cells when it was at 10% of cells. The errors have been corrected in the latest online HTML and PDF versions of the article. The authors regret the errors.
MEDI0457 Plus Durvalumab in HPV-associated HNSCC—Letter
Authors: Keita Mori, Akifumi Notsu, Keita Miura, Yusuke Onozawa
Journal: Clinical Cancer Research (2023)

We read with interest the article by Aggarwal and colleagues (1). The authors should be congratulated on the well-designed phase Ib/IIa trial to investigate the safety and efficacy of the combination treatment of MEDI0457 and durvalumab in human papillomavirus–associated recurrent/metastatic head and neck squamous cell carcinoma. They concluded that MEDI0457 plus durvalumab was well tolerated, but the primary efficacy endpoint was not reached. We think that the authors can say that primary efficacy was met because of the reason described below.As the primary endpoint, the objective response rate (ORR) was evaluated. The authors planned to test the null hypothesis that the ORR was less than or equal to 15% with a one-sided significance level of 10%. In terms of a confidence interval (CI), the null hypothesis is rejected if the lower limit of the two-sided CI for ORR with the confidence coefficient of 80% is more than 15%.In the result of the trial, the ORR was 27.6% (8/29), 80% CI was 16.8% to 40.9% calculated by the Clopper–Pearson method, and the lower limit was more than 15%. Then the null hypothesis can be rejected and the authors could say that the primary endpoint is met.Of course, it is important to output 95% CIs for comparison with other studies, such as systematic reviews that include nonrandomized studies. For this purpose, the 95% CI and the 80% CI or lower limit that have already been output may be written together.See the Response, p. 2736K. Mori reports personal fees from Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Daiichi Dankyo Co., Ltd., and Eli Lilly Japan K.K. outside the submitted work. K. Miura reports personal fees from Chugai Pharmaceutical and Taiho Pharmaceutical outside the submitted work. No disclosures were reported by the other authors.
Loss of the Atrial Fibrillation-Related Gene, <i>Zfhx3</i> , Results in Atrial Dilation and Arrhythmias
Authors: Heather S. Jameson, Alan Hanley, Matthew C. Hill, Ling Xiao, Jiangchuan Ye, Aneesh Bapat, Elsa Ronzier, Amelia Weber Hall, William J. Hucker, Sebastian Clauss, Miranda Barazza, Elizabeth Silber, Julie A. Mina, Nathan R. Tucker, Robert W. Mills, Jin-Tang Dong, David J. Milan, Patrick T. Ellinor
Journal: Circulation Research (2023)

ZFHX3 (zinc finger homeobox 3), a gene that encodes a large transcription factor, is at the second-most significantly associated locus with atrial fibrillation (AF), but its function in the heart is unknown. This study aims to identify causative genetic variation related to AF at the ZFHX3 locus and examine the impact of Zfhx3 loss on cardiac function in mice. CRISPR-Cas9 genome editing, chromatin immunoprecipitation, and luciferase assays in pluripotent stem cell-derived cardiomyocytes were used to identify causative genetic variation related to AF at the ZFHX3 locus. Cardiac function was assessed by echocardiography, magnetic resonance imaging, electrophysiology studies, calcium imaging, and RNA sequencing in mice with heterozygous and homozygous cardiomyocyte-restricted Zfhx3 loss (Zfhx3 Het and knockout, respectively). Human cardiac single-nucleus ATAC (assay for transposase-accessible chromatin)-sequencing data was analyzed to determine which genes in atrial cardiomyocytes are directly regulated by ZFHX3. We found single-nucleotide polymorphism (SNP) rs12931021 modulates an enhancer regulating ZFHX3 expression, and the AF risk allele is associated with decreased ZFHX3 transcription. We observed a gene-dose response in AF susceptibility with Zfhx3 knockout mice having higher incidence, frequency, and burden of AF than Zfhx3 Het and wild-type mice, with alterations in conduction velocity, atrial action potential duration, calcium handling and the development of atrial enlargement and thrombus, and dilated cardiomyopathy. Zfhx3 loss results in atrial-specific differential effects on genes and signaling pathways involved in cardiac pathophysiology and AF. Our findings implicate ZFHX3 as the causative gene at the 16q22 locus for AF, and cardiac abnormalities caused by loss of cardiac Zfhx3 are due to atrial-specific dysregulation of pathways involved in AF susceptibility. Together, these data reveal a novel and important role for Zfhx3 in the control of cardiac genes and signaling pathways essential for normal atrial function.
Platelet‐Rich Plasma Composite Organohydrogel with Water‐Locking and Anti‐Freezing to Accelerate Wound Healing
Authors: Chao Cai, Huimin Zhu, Yujie Chen, Xiuqun Yuan, Hezhou Liu, Zhi Yang
Journal: Advanced Healthcare Materials (2023)

Abstract Hydrogels have gained impressive attention in biological medicine due to their excellent biosafety, softness, and varied functional components. However, conventional hydrogels have inherent defects, such as low tensile strength, weak water‐locking, and poor anti‐freezing. In tissue engineering, once the hydrogel loses water or freezes, it will harden the interaction interfaces and destroy the nascent granulation tissue. Herein, based on the design concept of “hard frame−soft penetration”, a composite adhesive organohydrogel is fabricated by introducing bacterial cellulose and platelet‐rich plasma (PRP) into a poly‐ N ‐( tris [hydroxymethyl]methyl)acrylamide (THMA)/ N ‐acryloyl aspartic acid (AASP) hybrid gel network infiltrated with glycerol/water binary solvent. The resultant organohydrogels exhibit excellent antifreeze properties at low temperatures (−80 °C) and demonstrate stable long‐term water retention (91%) in the open environment within 12 days and can adhere firmly to the tissues by the action of “hydrogen bond clusters”. Additionally, the introduction of bacterial cellulose matrix endows the organohydrogel with high tensile strength similar to that of skin. In vivo, the PRP‐loaded organohydrogel can release a variety of growth factors to accelerate the wound healing process through collagen deposition and angiogenesis. Altogether, this strategy will extend the life of the hydrogel in some harsh medical environments.
“Severity” in adult sickle cell disease
Authors: Martin H. Steinberg, Mark T. Gladwin
Journal: American Journal of Hematology (2023)

Martin H. Steinberg is a consultant for Fulcrum Therapeutics, Cellarity, and Vertex Pharmaceuticals. He is a member of the Steering Committee for the gene therapy trial of CTX001 (exa-cel) sponsored by Vertex. Mark T. Gladwin is a co-inventor of patents and patent applications directed to the use of recombinant neuroglobin and heme-based molecules as antidotes for CO poisoning, which have been licensed by Globin Solutions, Inc. Dr. Gladwin is a shareholder, advisor, and director in Globin Solutions, Inc. Dr. Gladwin is also co-inventor on patents directed to the use of nitrite salts in cardiovascular diseases, which were previously licensed to United Therapeutics, and is now licensed to Globin Solutions and Hope Pharmaceuticals. Dr. Gladwin is a principal investigator in a research collaboration with Bayer Pharmaceuticals to evaluate riociguate as a treatment for patients with SCD. None.